This invention relates to dentifrice compositions and, more particularly, to antiseptic dentifrice compositions containing Beta-D-glucose and glucose oxidase for producing hydrogen peroxide in situ during oral application of the dentifrice.
Dentifrices, in powder, paste, cream and liquid forms, are used for both cosmetic and therapeutic purposes. Consistent with these purposes, dentifrices are formulted to contain active ingredients such as cleansing and polishing materials, as well as various antibacterial and anticaries agents for use as aids in the prevention of tooth decay.
It is generally understood in the dental art that certain kinds of tooth decay are initiated by acid etching of the tooth enamel with the source of the acid being a metabolite resulting from bacterial and enzymatic action on food particles in the oral cavity. It is generally accepted that plaque--which is a soft accumulation on the tooth surfaces consisting of an organized structure of microorganisms, proteinaceous and carbohydrate substances, epithelial cells, and food debris--is a contributory factor in the development of various pathological conditions of the teeth and soft tissue of the oral cavity. It has been suggested that the saccharolytic organisms of the oral cavity, which are associates with the plaque cause decalcification beneath the plaque matrix through metabolic activity which results in the accumulation and localized concentration of organic acids. The etching and decalcification of the enamel may continue until the pulp chamber of the tooth is reached.
A wide variety of materials have been considered for use as decay-preventative agents in dentifrice compositions. Some of the substances which have been so considered include para-aminobenzoic acid, a combination of urea and urease to produce ammonia during oral application of the dentifrice, chlorophyll, perflourinated long chain organic compounds, complex iodine, penicillin, benzohydroxamic acid, and glucose oxidase to produce hydrogen peroxide during oral application of the dentifrice.
U.S. Pat. No. 2,526,614 (Butterfield, 1950) discloses the incorporation into a dentifrice of an enzyme system comprising urea and urease which produces ammonia in the presence of moisture that is encountered during oral application of the dentifrice. The patentee reports that the action of the ammonia together with residual urea is bacterocidal to acidogenic organisms and antienzymatic to the production of lactic acid by such organisms. In addition, it is pointed out that the action of ammonia produced from this enzyme system dissolves mucin plaques.
U.S. Pat. No. 3,427,380 (Kirkland, 1969) discloses that oral organisms produce a capsular material which is a factor in holding plaque together and allowing its further growth and that the oral application of a dentifrice containing para-aminobezoic acid inhibits capsule formation by such organisms and thereby retards the development of dental plaque without inhibiting the growth of these organisms.
U.S. Pat. No. 3,137,634 (Schiraldi, 1964) discloses that the oral application of a dentifrice composition containing, for example, potassium copper chlorophyllin, dicalcium phosphate and tetrasodium pyrophosphate is useful in the treatment of gum diseases such as periodontal disorders like gingivitis, pyorrhea and trench mouth and, in addition, reduces undesirable breath odors.
U.S. Pat. No. 3,227,618 (Dunellen, 1966), in the background portion of the specification, recites that it has been disclosed that treatment of tooth enamel with a mixture of stannous flouride, hydrogen peroxide and insoluble sodium metaphosphate increases the enamel hardness as described in The Journal of the American Dental Association, May, 1950, Vol. 40, pg. 513-519.
U.S. Pat. No. 3,574,824 (Echeandia, et al., 1971) discloses an anhydrous toothpaste base to which can be added enzymes identified as proteases, polysaccharidases, and lipases for the purpose of retarding plaque formation through the breakdown of ingested proteins, carbohydrates and fats.
Merck Index, 9th Edition, 1976, at page 633, discloses that hydrogen peroxide solution 3% contains 2.5-3.5 wt. % of hydrogen peroxide which is equivalent to 8-12 volumes of oxygen, and that this solution is a topical anti-infective which is useful in pharmaceutical preparations such as mouthwashes, dentifrices, and sanitary lotions.
U.S. Pat. No. 4,150,113, (Hoogendoorn et al., 1979) discloses an enzymatic dentifrice containing glucose oxidase which acts on glucose present in saliva and tooth plaque to produce hydrogen peroxide. The patentees, after noting that oral bacteria effect glycolysis of food products containing sugars through bacterial enzyme systems having SH-groups, point out that lactoperoxidase, which is present in saliva, provides the means for transferring oxygen from hydrogen peroxide to the oral bacteria resulting in the oxidation of the SH-containing enzymes into inactive disulfide enzymes. It is further disclosed that the dentifrice may be formulated with potassium thiocyanate.
Hoogendoorn, et al., Carries Research, 11:77-84, 1977 disclose that the hypothiocyanate ion is the bacterial inhibitor formed by the system containing lactoperoxidase, thiocyanate and hydrogen peroxide.
U.S. Pat. No. 4,269,822 (Pellico et al., 1981) discloses an antiseptic dentifrice containing an oxidizable amino acid substrate and an oxidoreductase enzyme specific to such substrate for producing hydrogen peroxide and ammonia upon oral application of the dentifrice, with pre-application stability being maintained by limiting the quantity of any water present in the dentifrice.
U.S. Pat. No. 2,891,868 (Heggie, 1959) discloses that chewing gum which is formulated with an oxygen sensitive flavoring agent can be protected against oxidative deterioration of the flavoring agent by incorporating into the formulation an enzyme system containing glucose, glucose oxidase and catalase, and that this protection is effective in the presence of bound water only and does not require free water.
Commercial glucose oxidase which also contains catalase is promoted to the food and beverage industry as an agent for protecting their susceptible packaged products against deterioration in the presence of oxygen and/or glucose by effecting an enzymatic in situ reaction which results in the consumption of oxygen and glucose with the ultimate end product of the enzymatic reaction being gluconic acid.
The effectiveness of a glucose oxidase dentifrice (U.S. Pat. No. 4,150,133) as a bacterial inhibitor through an enzymatic reaction upon oral application is dependent, to a significant extent, upon the subsisting oral concentration of glucose at the time of the oral application of the dentifrice. The concentration of glucose supplied by saliva varies as a direct function of its biological production and salivary flow. Thus, when salivary flow is at a diminished level either as a natural event or as an event arising out of certain types of medical treatment, the oral concentration of glucose will be correspondingly reduced which, in turn, is a limiting factor in the oral production of hydrogen peroxide, a precursor of the hypothiocyanate bacterial inhibitor. It is generally reported in the literature that the mean salivary glucose concentration in adults is about 0.1 millimoles per liter (or about 0.0001 millimoles per gram). Accordingly, it would be advantageous to provide a package and shelf stable, enzymatic dentifrice containing glucose oxidase and Beta-D-glucose at suitable concentration levels for generating reasonably predictable amounts of hydrogen peroxide upon oral application of the dentifrice and thereby overcome the uncertainties associated with the use of a glucose oxidase dentifrice that relies upon salivary glucose as the source of the substrate for the hydrogen peroxide generating reaction.